Synihesis And Performance Of The Redox-responsive Drug Delivery Carrier

Recently,nano-drug carrier has been more and more attention because it has many characteristics including high drug loading,targeting,specificity,controlled release rate and prolonged circulation in the bloodstream,especially the redox-responsive nano-carrier.When the redox-responsive nano-drug carrier containing anti-tumor drugs come into the body,it is very stable in the blood circulation under normal circumstances,but its structure will be changed when suffer from reducing agent and the drug is quickly release from nano-carrier.Consequently,in this article,two kinds of redox-responsive nano-carrier were designed and synthesized,all the work as follows :(1)The triblock copolymers mPEG-b-PAGESH-b-PLLA were synthesized by combining ring-opening polymerization and thiol-ene click chemistry under light,and hydrophilic polyethylene glycol(mPEG),allyl glycidyl ether(AGE)and hydrophobic lactide(LA)as materials.And then high stability of the redox-responsive cross-linked micelles were prepared,when mercapto groups are oxidized into disulfide bonds in the presence of hydrogen peroxide.The polymer molecular structures and molecular weight distribution were characterized by 1HNMR and GPC.At the same time,the data of the dynamic light scattering(DLS),fluorescence spectrum(FL)and transmission electron microscopy(TEM)showed that the shorter hydrophobic segments of polymer was,the higher critical micelle concentration(CMC)was,and the smaller particle size was.In addition,the in vitro release of drug-loaded micelles showed that the drug release behavior of cross-linked micelles was significantly accelerated in the presence of the reducing agent DTT.Therefore,this redox-responsive cross-linked micelles containing disulfide bonds are expected to be a responsive nano-carrier.(2)In this paper,we describe the synthesis and performance of redox-responsive nano-drug carrier HNTs-SS-PLLA-sc-PDLA-b-mPEG and HNTs-SS-PDLA-b-mPEG based on halloysite nanotube linked to the polymer by a series of reactions.First of all,we modified the halloysite nanotube with(3-mercaptopropyl)trimethoxysilane,2,2-dithiodipyridine and 3-mercaptopropionic acid,so that introducing functional groups,such as carboxyl groups and disulfide bonds,and then grafted by different types of polymers by esterification reaction and sterecomplex.The chemical structures of the halloysite nanotubes were analyzed by SEM and FT-IR.Studies on the dispersion of the halloysite nanotubes before and after modification showed that the dispersion of the modified HNTs was significantly improved.Forthermore,the in vitro release indicated that disulfide-containing HNTs of the grafted polymers can rapidly release doxorubicin in the presence of the reducing agent DTT.Therefore,there is great application prospect for the redox-response halloysite nanotubes as a nano-drug carrier.